A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)
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|ClinicalTrials.gov Identifier: NCT03730012|
Recruitment Status : Recruiting
First Posted : November 5, 2018
Last Update Posted : July 18, 2019
The purpose of this study is to determine the safety and tolerability of gilteritinib given in combination with atezolizumab in participants with relapsed or treatment refractory FMS-like tyrosine kinase 3 (FLT3) mutated AML and to determine the composite complete remission (CRc) rate for participants who either discontinued the study or completed 2 cycles of gilteritinib given in combination with atezolizumab.
This study will also evaluate pharmacokinetics (PK), response to treatment, remission and survival. Adverse events (AEs), clinical laboratory results, vital signs, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status scores will also be assessed.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation||Drug: gilteritinib Drug: atezolizumab||Phase 1 Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
This study will have 2 phases.
The phase 1 portion of this study is to establish the recommended phase 2 dose (RP2D) of gilteritinib given in combination with atezolizumab.
The phase 2 portion of the study will treat patients with gilteritinib and atezolizumab at the RP2D and will enroll in two stages. The first stage will evaluate the remission rate and if a minimum rate is achieved, a second stage of enrollment will continue.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2 Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FLT3 Mutated Acute Myeloid Leukemia (AML)|
|Actual Study Start Date :||May 24, 2019|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||August 2022|
Experimental: Gilteritinib plus Atezolizumab
Participants will be treated with gilteritinib once daily for the phase 1 portion of the study to establish the recommended dose for the phase 2 portion. In the phase 2 portion, the participants will be treated with gilteritinib once daily at dose determined by the phase 1 portion of the study. Atezolizumab will be administered once every 2 weeks for the phase 1 and 2 portions of the study. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet 1 of the discontinuation criteria; whichever occurs first.
Gilteritinib is administered orally
Other Name: ASP2215
Atezolizumab is administered by intravenous infusion
- Dose Limiting Toxicities (DLT) - (phase 1) [ Time Frame: Up to 28 days ]Incidence of dose limiting toxicities
- Composite complete remission (CRc) rate (phase 1 and phase 2) [ Time Frame: Up to 56 days (2 cycles of treatment) ]
Number of participants with CRc. CRc is defined as a complete remission (CR), complete remission without platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi).
CRc rate is defined as the rate of all complete and incomplete remission (i.e., CR + CRp + CRi).
- PK of Gilteritinib in plasma: (Ctrough) [ Time Frame: Up to 6 months ]Ctrough will be derived from pharmacokinetic (PK) plasma samples collected.
- Complete Remission (CR) rate [ Time Frame: Up to 3 years ]Number of participants with complete remission (CR)
- Best Response rate (CRc + partial remission [PR]) [ Time Frame: Up to 3 years ]Best response is defined as the best-measured response (CR, CRp, CRi or PR) post-treatment.
- Duration of remission [ Time Frame: Up to 3 years ]
Duration of remission is defined as time from date of first CRc, CR, CRi, CRp, and response (CRc + PR) until the date of documented relapse.
Duration of remission includes duration of CRc, CR, CRi, CRp and response (CRc + PR).
- Event Free Survival (EFS) [ Time Frame: Up to 3 years ]EFS is defined as the time from the date of enrollment until the date of documented relapse from CR, CRp or CRi, treatment failure or death from any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Up to 3 years ]OS is defined as the time from the date of enrollment until the date of death from any cause. For a subject who is not known to have died by the end-of-study follow-up, OS is censored at the date of last contact.
- Complete Remission (CR) rate with partial hematologic recovery (CRh) [ Time Frame: Up to 3 years ]Number of participants with complete remission (CR) with partial hematologic recovery (CRh)
- Safety assessed by Adverse Events [ Time Frame: Up to 3 years ]An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
- Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]Number of participants with potentially clinically significant laboratory values
- Number of participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]Number of participants with potentially clinically significant vital sign values.
- Safety assessed by 12-lead electrocardiogram (ECG) [ Time Frame: Up to 3 years ]12-lead ECGs will be recorded in triplicate (3 separate ECGs, 10 minutes resting prior to first ECG and at least 5 minutes apart per time point) and transmitted electronically for central reading. The mean of the triplicate ECG from central read will be used for all final treatment decisions and adverse event reporting.
- Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance score [ Time Frame: Up to 3 years ]ECOG performance status measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead. 0=Best status; 5=Worst status.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03730012
|Contact: Astellas Pharma Global Developmentfirstname.lastname@example.org|
|United States, California|
|Ronald Reagan UCLA Medical Center||Recruiting|
|Los Angeles, California, United States, 90095|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60037|
|United States, New York|
|Roswell Park Cancer Institute (RPCI)||Recruiting|
|Buffalo, New York, United States, 14263|
|United States, Ohio|
|The Ohio State University Comprehensive Cancer Center (OSUCCC)||Recruiting|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|Vanderbilt Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Study Director:||Executive Medical Director||Astellas Pharma Global Development|